Bacterial meningitis is a significant cause of mortality and morbidity, especially in infants and young children. Although 85-95% of persons contracting meningitis currently survive, significant neurological sequelae occur in approximately one-third of these long-term survivors. The objective of the proposed research is to investigate the pathogenesis and prevention of Haemophilus influenzae meningitis. These studies will utilize an animal model. Our previous and continuing investigations have shown that intranasal inoculation of infant rats with Haemophilus influenzae type b results in bacteremia and meningitis. The histologic characteristics of the meningitis, the GSF findings and the age-related susceptibility of infant rats to sepsis and meningitis resemble the disease as it occurs in infants and children. Our present goal is to investigate the pathogenicity of type b as opposed to encapsulated non-type b strains of H. influenzae. These studies will be pursued by (1) obtaining isogenic strains by means of genetic exchange through bacterial transformation, (2) in vivo comparison of the potential of these isogenic strains to colonize the nasopharynx, invade the bloodstream and cause meningitis in the rat model.